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@ARTICLE{KlingerKnig:140563,
author = {Klinger-König, Johanna and Hertel, Johannes and Van der
Auwera, Sandra and Frenzel, Stefan and Pfeiffer, Liliane and
Waldenberger, Melanie and Golchert, Janine and Teumer,
Alexander and Nauck, Matthias and Homuth, Georg and Völzke,
Henry and Grabe, Hans J},
title = {{M}ethylation of the {FKBP}5 gene in association with
{FKBP}5 genotypes, childhood maltreatment and depression.},
journal = {Neuropsychopharmacology},
volume = {44},
number = {5},
issn = {0893-133X},
address = {Basingstoke},
publisher = {Nature Publishing Group71819},
reportid = {DZNE-2020-06885},
pages = {930-938},
year = {2019},
abstract = {DNA methylation of the FKBP5 gene is assumed to alter FKBP5
expression and hence the synthesis of the FK506 binding
protein 51, a central element of a genomic negative feedback
loop for glucocorticoid receptor signaling. The present
study aimed to replicate and extend previously reported
influences of FKBP5 genotypes, childhood maltreatment and
depression on methylation levels of five CpG sites in intron
7 of the FKBP5 gene in a large population-based sample.
Besides the single nucleotide polymorphism (SNP) rs1360780,
associations of the FKBP5 methylation with 22 other,
unlinked FKBP5 SNPs as well as associations between FKBP5
methylation levels and transcription levels were
investigated. Using whole-blood methylation of 3965 subjects
of the Study of Health in Pomerania (SHIP) reduced
methylation levels in TT allele carriers of rs1360780
(OR = 0.975, p = .005) and currently depressed
subjects (OR = 0.995, p = 0.005) were found.
Further, an impact of two yet undescribed SNPs (rs6910300,
rs7771727) on methylation levels was observed. However, main
and interactive effects for childhood maltreatment and
lifetime major depressive disorder observed in previous
studies could not be replicated. Finally, FKBP5 methylation
levels were not related to FKBP5 transcription levels in
whole blood. Thus, the present study verified the
associations of FKBP5 genotypes and state depression on the
FKBP5 methylation levels of five CpG sites in intron 7.
However, FKBP5 methylation of these five CpG sites could not
be validated as a valuable clinical biomarker for biological
long-term effects of childhood maltreatment or lifetime
depression.},
keywords = {Adult / Adult Survivors of Child Abuse: statistics $\&$
numerical data / Adverse Childhood Experiences: statistics
$\&$ numerical data / Aged / DNA Methylation: genetics /
Depressive Disorder: epidemiology / Depressive Disorder:
etiology / Depressive Disorder: genetics / Female /
Follow-Up Studies / Germany: epidemiology / Humans / Male /
Middle Aged / Registries / Tacrolimus Binding Proteins:
genetics / Young Adult / Tacrolimus Binding Proteins (NLM
Chemicals) / tacrolimus binding protein 5 (NLM Chemicals)},
cin = {AG Grabe},
ddc = {610},
cid = {I:(DE-2719)5000001},
pnm = {344 - Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30700816},
pmc = {pmc:PMC6461917},
doi = {10.1038/s41386-019-0319-6},
url = {https://pub.dzne.de/record/140563},
}